Burden of respiratory syncytial virus in adults in the United Kingdom: A systematic literature review and gap analysis

Abstract Despite the growing recognition of a potentially significant respiratory syncytial virus (RSV) disease burden in adults, relevant evidence in the United Kingdom (UK) is limited. This systematic literature review (SLR) aimed to identify the disease burden of RSV in UK adults, including certain high‐risk subgroups and existing evidence gaps. Published studies (2011 onwards) reporting epidemiological, economic and clinical burden outcomes in UK adults (≥15 years) with RSV were identified from indexed databases, including MEDLINE, Embase and the Cochrane library. High‐risk groups included elderly (≥65 years), immunocompromised, co‐morbid and co‐infected patients. Outcomes included RSV incidence/prevalence, mortality, clinical presentation and direct/indirect resource use/costs. Twenty‐eight publications on 28 unique studies were identified, mostly in general/respiratory indicator (n = 17), elderly (n = 10) and immunocompromised (n = 6) cohorts. Main outcomes reported in the general/respiratory indicator cohort were RSV infection incidence (seasonal/annual: 0.09–17.9%/6.6–15.1%), mortality (8,482 deaths/season) and direct resource use (including mean general practitioner [GP] episodes/season: 487,247). Seasonal/annual incidence was 14.6–26.5%/0.7–16% in high‐risk cohorts. Attributed to RSV in the elderly were 7,915 deaths/season and 175,070 mean GP episodes/season. Only two studies reported on co‐morbid cohorts. Clinical burden outcomes were only reported in general and immunocompromised patients, and no evidence was found in any cohort on indirect economic burden or RSV complications. Evidence captured suggests that RSV may have a substantial burden in UK adults. However, available data were limited and highly heterogenous, with further studies needed to characterise the burden of RSV in adults and to validate our findings.


| INTRODUCTION
There are a number of respiratory viruses causing seasonal epidemics in the United Kingdom (UK).The most broadly studied and commonly known of these viruses is influenza, which is known to have substantial morbidity and mortality. 1A modelling study found that around 28,500 hospitalisations and over 7,100 deaths were attributable to influenza in a mean season in the UK between 1996 and 2009, and the highest incidence rates of hospitalisations and death were found in the elderly population (≥75 years). 2 As such, efforts to prevent or ameliorate the impact of seasonal influenza have resulted in a well-established vaccination programme targeting high-risk populations in the UK, including the elderly population (aged ≥65 years), co-morbid patients (e.g., chronic respiratory disease) and the immunocompromised. 3 contrast, notably less information is published on other seasonal respiratory viruses, such as respiratory syncytial virus (RSV), despite the growing recognition of a potentially considerable disease burden comparable to influenza. 40][11] Patient groups known to be at higher risk of severe disease include the elderly population, as well as co-morbid, immunocompromised and co-infected patient populations. 12e burden of RSV is commonly discussed in the context of childhood infections.It was estimated that around 29,160 hospitalisations and 83 deaths among children and adolescents aged 0-17 years were attributable to RSV in the UK in an average season between 1995 and 2009, with the highest proportion of this burden in infants <6 months of age. 13However, studies suggest that the burden of RSV in adults may also be substantial. 14,15A modelling study for RSV estimated around 17,800 hospitalisations and almost 8,500 deaths were attributable to RSV in an average season in the UK between 1995 and 2009 among adults (≥18 years), with the highest disease burden in the elderly population (93% of deaths in adults occurred in patients ≥65 years). 14Another study estimated that RSV accounted for a seasonal annual average of 71 hospitalisations per 100,000 in adults aged 65-74 years and 251 admissions per 100,000 in adults aged ≥75 years between 2010 and 2017 in England. 15spite the burden of RSV highlighted above, there are currently very few therapies available in the UK.[18][19][20][21] In addition, nirsevimab has recently been approved by the Medicines and Healthcare products Regulatory Agency (MHRA). 225][26][27][28] Thus, understanding the burden of RSV in adult populations will be critical to appraise the upcoming therapeutic and preventative modalities.
0][31] As such, there still remains a need to strengthen the current evidence base on the burden of RSV, particularly in UK adults, to adequately inform assessment of new vaccines and treatments in the UK.Thus, the present SLR set out to characterise the clinical, economic and epidemiological burden of RSV in UK adults, including those at higher risk of severe disease, and to conduct a gap analysis to highlight areas that would benefit from further research.

| METHODS
This SLR was performed in accordance with a pre-specified protocol, although this was not registered, and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. 32SV combined with a validated UK geographical filter. 33Additionally, conference proceedings of relevant congresses that had taken place between 2019 and 2021 in the original SLR, and any conducted since the original SLR in the SLR update (2022), were screened for relevant research studies, and economic/HTA websites were manually hand-searched for relevant records.Bibliography searching of identified SLRs, network meta-analyses, economic evaluations and HTAs was also carried out.The full search strategy is described in Appendix S1 (Tables S1-S9).

| Study selection
The eligibility criteria in Table 1 were used to identify studies relevant to this review.The population of interest comprised adults (≥15 years) with RSV infection, including, but not limited to, the high-risk subgroups analysed in this SLR (elderly population [≥65 years], patients with co-morbidities or co-infection and immunocompromised patients).The outcomes of interest included epidemiological, economic and clinical burden outcomes.The studies included in this SLR were observational studies, and no intervention or comparator limits were applied.Due to the aims of this review, only studies conducted in the UK were included, and for this reason, it was considered acceptable to only review publications in the English language.The date limits applied were 2011 for journal articles and 2019 for conference abstracts, in order to only include information relevant to the current disease and treatment landscape.
The titles and abstracts of publications identified from the database searches were reviewed by two independent reviewers against the eligibility criteria.Where the applicability of the inclusion criteria was unclear, the article was included for full-text screening.The full-text publication of each record deemed eligible (or unclear) was further reviewed against the eligibility criteria by two independent reviewers.In cases where insufficient information was provided to adequately assess eligibility, the publication was excluded at the fulltext stage.Hand searching of conference proceedings, economic/HTA websites and bibliographies of the identified SLRs were conducted by a single reviewer with decisions regarding eligibility checked by a second reviewer.Any disagreements were resolved by discussion until a consensus was met.If necessary, a third independent reviewer made the final decision.Full lists of studies included in the SLR and excluded at the full-text stage review, including the reasons for exclusion, are provided in Appendix S2 (Table S10) and Appendix S3 (Tables S11-S12), respectively.
Key information from all included studies was extracted into a pre-specified data extraction grid in Microsoft Excel; extracted information included characteristics of the patient population, study characteristics and the relevant outcome data presented.Data extraction was conducted by a single reviewer, and data were independently verified by a second reviewer.Where relevant, graphical data digitisation was performed using Digitizelt software; digitisation was not performed for continuous data.
A gap analysis was additionally conducted to identify subgroups of interest and burden outcomes where little or no data exist in the literature.The analysis was completed by one individual and independently verified by another individual.

| Risk of bias
Quality assessments of included studies were also conducted using the quality assessment tool developed by The Alberta Heritage Foundation for Medical Research (AHFMR). 34Study quality assessment was conducted by a single reviewer and independently verified by a second reviewer.

| Search results
In the original SLR, a total of 2,507 records were retrieved by the electronic database searches, and an additional 635 were captured by supplementary searches of conference abstracts and economic/HTA websites.Of these, 22 publications reporting on 22 studies were found to fulfil the eligibility criteria for inclusion in this review.
In the SLR update, a total of 253 novel records were retrieved by the electronic database searches and a further 327 captured by supplementary searches of conference abstracts and economic/HTA websites.Of these, six publications reporting on six studies were found to fulfil the eligibility criteria for inclusion in the review.
In total, 28 studies were identified in the original SLR and SLR update.The PRISMA diagram for the SLR update is provided in Figure 1 and for the original SLR in Appendix S4.
Only one study was identified reporting RSV infection incidence in a general cohort.Ponsford et al. 48compared healthy controls with immunocompromised patients with primary antibody deficiency.
Among healthy controls, the study found a very low measured annual RSV infection incidence of 0.3% (n = 38; number of swabs taken n = 626).
F I G U R E 2 Incidence of RSV in patients with a respiratory indicator.Italicised values were manually calculated; data from relevant studies identified in this SLR that only represented RSV infection incidence graphically and/or used units other than percentage 43,44,53,55 are not included in this figure.Abbreviations: A, annual; ICU, intensive care unit; PCR, polymerase chain reaction; POCT, point-of-care testing; S, seasonal.
One study reported estimated RSV-attributable mortality in a respiratory indicator cohort, assessing adult patients diagnosed with RSV in the UK-wide Office for National Statistics database. 14The study found a total of 8,482 deaths per season were attributable to RSV between 1995 and 2009.Among all deaths attributable to respiratory disease, 4.2% and 5.9% for the 18-49 and 50-64 age group, respectively, were estimated to be attributable to RSV.
Clinical burden evidence was identified in only one study, 48  Four studies that reported economic burden outcomes in a general population and/or patients with a respiratory indicator reported direct resource use across various settings of care, including GP visits, inpatient hospital stays and telehealth calls (see Appendix S5 for results). 14,54,55,59,60 the studies assessing patients with a respiratory indicator, two reported GP visits, with one estimating the mean number of weekly GP consultations attributed to RSV between 2011 and 2015. 14,59rbey et al. 59

| Burden of RSV in elderly patients
Among the high-risk subpopulations, the largest body of UK evidence was found for the elderly population (≥65 years).The elderly are known to be at a higher risk of serious illness from RSV and other respiratory viruses, owing to higher rates of co-morbidities and lower immunity when compared with a younger patient population. 61n studies identified in this SLR reported on an elderly cohort (aged ≥65 years). 14,15,37,38,43,51,53,55,59,60Characteristics of these studies and extracted outcomes are described in Appendix S5 (Table S14).
Seven studies reported on epidemiological burden in the elderly. 14,37,38,43,51,53,55Of these six studies captured RSV incidence in patients ≥65 years 37,38,43,51,53,55 and two studies in patients ≥75 years. 37,55seasonal RSV incidence of 26.5% was reported in one study that collected data from hospitals and GPs in the West Midlands region of England during the 2009/2010 influenza pandemic (≥65 years). 51Other studies reported on annual incidence rates in this population, which were considerably lower.The average annual incidence in patients ≥65 years ranged between 1.4% (myocardial infarction [MI] patients, 65-74 years 37 ; hospital settings) and 3.91% (≥65 years 38 ; GP settings) (Figure 3).In the former, RSV incidence was reported in elderly patients with co-morbidity, where in the latter, incidence was reported in patients presenting with influenza-like illness. 37,38ve studies captured in the SLR assessed the incidence of RSV across different age groups, with all finding the incidence of RSV increasing with older age. 38,42,43,51,55For example, Johannesen et al. 55 estimated incidence rates per 1,000 patients in England aged between 18-64 (0.1), 65-74 (0.9), 75-84 (2.8) and ≥85 years (6.0).
One study reporting modelled annual (continuous) incidence rates in patients aged ≥75 years with RSV following MI and stroke admission found incidence rates to be lowest in patients with stroke (0.7%) and the highest in patient presenting with MI (1.7%). 37Another study modelling annual (continuous) incidence rates per 1,000 patients found rates to be highest in the 75-84 (England: 2.8; Scotland: 3.0) and ≥85 (England: 6.0; Scotland: 5.0) age groups compared with the 65-74 group (England: 0.9; Scotland: 0.6). 55e study presented data for a cohort with a respiratory indicator from both GP and hospital settings, finding 93% of all deaths attributable to RSV occurred in elderly patients (≥65 years old). 14 studies reflecting the clinical burden of RSV in the elderly population were found in this SLR.
F I G U R E 3 Incidence of RSV in elderly patients.Data from relevant studies identified in this SLR that only represented RSV infection incidence graphically and/or used units other than percentage 43,44,53,55 are not included in this figure.Abbreviations: A, annual; NR, not reported; RSV, respiratory syncytial virus; S, seasonal.
All five of the studies reporting economic burden outcomes in an elderly population reported direct resource use.

| Burden of RSV in other high-risk patient groups
Other high-risk groups investigated in this review included co-morbid, immunocompromised and co-infected patient populations, as they are known to be at a higher risk of morbidity from respiratory infections. 12Characteristics of the studies reporting on these patient subgroups, as well as extracted outcomes for all studies, are provided in Appendix S5 (Tables S15-S17).
For the co-morbid patient population, the evidence was highly limited, with only two studies identified. 37,39Both studies in a hospital setting reported an annual RSV infection incidence of 0.7% (≥75 years, stroke patients 37 ) and 2% (≥18 years, cystic fibrosis patients 39 ) (Figure 4).No discernible trends were observed across the results reported for co-morbid patient populations, based on the limited evidence identified.
Six studies reported on RSV infection incidence in immunocompromised patients. 35,41,45,47,48,56A wide range of RSV infection incidence rates (seasonal and annual) were reported (0.8-16%) (Figure 4). 41,47,56Four of the studies reporting on immunocompromised patient populations discussed RSV symptom presentation or symptom scores. 35,41,45,48As previously detailed, Ponsford et al. 48und that the immunocompromised cohort (n = 41) had a higher symptom load 7 days after RSV detection compared with the healthy controls with RSV (n = 38).Two other studies compared the incidence of upper and lower respiratory tract infections (URTIs and LRTIs) in RSV patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT).Balassa et al. 35 reported a slightly higher rate of drug usage and two reported inpatient stays, finding moderate resource use. 35,41,45ve studies reported on a co-infected patient population and presented the annual incidence of RSV in patients with invasive pneumococcal disease, leptospirosis, COVID-19 and community-acquired pneumonia. 38,40,50,57,58Incidence rates across these studies ranged from 0% (15-44 years, invasive pneumococcal disease; laboratory and database setting 38  burden evidence was identified for this patient subgroup.

| Gap analysis
The SLR identified a notable paucity of information on the burden of RSV in UK adults.The outcomes reported in all captured studies are summarised in Table 2.In order to explore the current evidence gaps systematically, a gap analysis framework was used, highlighting the need for further research on the burden of RSV in different adult populations (a summary of the gap analysis results is presented in Table 3; the full results can be found in Appendix S6).

| Quality assessment
A summary of the AHFMR quality assessment checklist results conducted for each study included in the SLR is detailed in Appendix S7 (Table S18).Overall, most included studies (23/28) were considered to have a low risk of bias.A total of five studies had a high risk of bias, measured as reporting high risk for 3 or more domains in the AHFMR checklist. 43,45,53,59,60

| DISCUSSION
The data found in this SLR on the disease burden of RSV in the UK adult population are highly heterogenous.As such, comparisons among studies should be interpreted with caution given several factors may have affected the estimates: methodological differences across studies, annual variations in RSV activity, data collection periods (seasonal versus annual), patient sampling methods, RSV testing methods, healthcare seeking behaviour of the underlying population and the impact of COVID-19 on the altered seasonality of RSV.
In addition, most studies in this SLR did not adjust for confounding, further complicating potential comparisons (Appendix S7).Due to these limitations, it was not feasible to conduct a meta-analysis of the studies included in this SLR.
Seasonal RSV infection incidence in patients with a respiratory indicator ranged between 0.09% and 17.9%, while annual incidence was between 6.6% and 15.1%. 49,51,54,56The results showed no discernible trend relating to study setting or RSV detection method.
However, variation in RSV infection incidence according to year of data collection was noted, which could be explained by variations in RSV incidence and/or testing behaviour.For instance, the lowest seasonal incidence (0.09%, patients ≥18 years, Poole et al. 49 ) was likely due to the social distancing measures imposed during the COVID-19 pandemic.The highest RSV infection incidence was reported during the 2009-2010 influenza pandemic, likely due to the increased testing behaviour for respiratory infections. 51nerally, RSV is believed to be underdiagnosed, especially in milder cases, due to low testing rates and non-specific symptoms, as well as the difficulty in adult diagnosis compared with children, due to insensitivity of diagnostic tests caused by a lower viral load in nasal secretions. 62Consequently, the higher seasonal incidence rates detected during the influenza pandemic may be hypothesised to be closer to the real RSV incidence. 9,12,62,63Interestingly, on the other hand, Blackburn et al. 37   that RSV has a slightly lower burden on the healthcare system than influenza, this still highlights the high number of GP episodes attributable to RSV in adults and consequently the high economic burden of RSV. 14,596][67] In addition, the captured studies discussing the T A B L E 2 Summary of outcomes reported by publication.
T A B L E 2 Summary of outcomes reported by publication.
Abbreviations: CRU, cost and resource use; RSV, respiratory syncytial virus.
economic burden of RSV focused on direct resource use, while information on costs and indirect resource use was not provided.
Among the high-risk populations, the largest body of evidence was found for the elderly patients.Similar to the general population, the incidence of RSV infections found in this sub-population was highly variable, with one study reporting the seasonal incidence of RSV infections in the West Midlands region of England in a hospital and GP setting among the patients ≥65 years as high as 26.5%, 51 and the annual incidence reported in other studies being considerably lower. 37,38This heterogeneity demonstrates that the measured incidence is linked to the data collection period (annual vs. seasonal, as well as the year of data collection) and the specific patient population.
Five studies captured in this SLR reported incidence data across different age groups and all found RSV infection incidence rates to increase across the age groups assessed with the highest rate reported in the elderly patient group (≥65 years).Importantly, the mortality in the elderly group was found to be substantial.One study found that for a cohort with a respiratory indicator from both GP and hospital settings, 8,482 deaths per season in adults (≥18 years) in the UK were attributed to RSV, and 93% of these deaths occurred in elderly patients (≥65 years); this mortality burden is substantial and comparable to that of influenza. 2,14number of studies were found reporting the burden of RSV in other high-risk groups, which in this SLR were defined as comorbid, immunocompromised and co-infected patient populations.
No discernible trends were observed across the results reported for co-morbid patient populations, based on the limited evidence identified.
For the immunocompromised patient population, a wide range of RSV infection incidence rates (seasonal and annual) were reported, ranging from 0.8% to 16%, suggesting that in some cases these patients might be more susceptible to RSV infection. 41,47,56ese results concur with the findings of a published SLR considering studies across global geographies, which found an incidence range of 2.1% to 19.6% in HSCT patients. 68The results of our SLR also suggest that immunocompromised patients may experience a higher symptom burden compared to healthy individuals, as well as present a substantial economic burden. 48,69milar to other patient groups, the identified evidence for coinfected patients was found to be heterogenous, which in some cases may be explained by a small sample size. 50e gap analysis highlighted that only a small number of studies, if any, report economic, epidemiological and/or clinical burden outcomes for each patient population of interest in this review.The lack of information was particularly notable for the clinical burden data and indirect economic data.Most studies captured are noncomparable, due to heterogeneity in study design, or differences in the patient group eligibility criteria.Due to the paucity of evidence identified in this SLR, it is difficult to fully interpret the public health and economic impact of RSV infections in the UK.Future nationally representative database analyses are required to fully assess the economic burden of RSV, and large, multicentre registry analyses are required to characterise the clinical burden of RSV.
This SLR was conducted in line with the Cochrane Handbook for Systematic Reviews of Interventions. 70A potential limitation of this review is that studies included were limited to being published in 2011 or later; however, this date limit was selected to ensure that only the data relevant to the current RSV landscape were identified.A further limitation is that the database search strategy was developed to capture studies that reported 'RSV' or 'respiratory syncytial virus' within the abstract, title or keywords.It is possible that studies assessing other viruses might have reported relevant burden data for RSV as a comparison within the full text and not specified this within the abstract.This limitation however was unavoidable, in order to ensure a manageable number of records were captured from the database searches.Another limitation of this SLR is that it included estimated/ modelled data alongside more robust measured data, which may weaken any of the conclusions that incorporate the modelled data.

| CONCLUSION
The data collected in this SLR show that the burden of RSV could be substantial and comparable to that of influenza, especially in high-risk populations.However, the available evidence is highly heterogenous, which precludes meta-analysis of the discovered data, and a high number of missed areas was identified by the gap analysis.There is clear need for further studies of RSV burden in the UK, particularly in light of RSV treatments and vaccines currently undergoing development, as well as advancements in diagnostics, in order to inform their future applications.
acknowledge David Slater, MMath; Evelyn Turner, BSc; and Faye Saville, MSci, from Costello Medical, UK, for support conducting the SLR and SLR update.Further, the authors acknowledge that some data reported in this manuscript have been published previously at the 12th International RSV Symposium 2022.

A
de novo SLR was conducted in October 2021, with an SLR update performed in August 2022.Electronic databases (MEDLINE, Embase, Database of Abstracts of Reviews of Effect [DARE], Cochrane Central Register of Controlled Trial [CENTRAL], Cochrane Database of Systematic Reviews [CDSR], National Health Service Economic Evaluation Database [NHS EED] and the International Health Technology Assessment [HTA] database [INAHTA]) were searched from database inception to 7 October 2021 in the original SLR and 8 August 2022 in the SLR update, using search terms for I G U R E 1 PRISMA diagram for the original SLR and SLR update.Abbreviations: CDSR, Cochrane Database of Systematic Reviews; CENTRAL, Cochrane Central Register of Controlled Trials; CRD, Centre for Reviews and Dissemination; DARE, Database of Abstracts of Reviews of Effects; HTA, Health Technology Assessment; INAHTA, International Health Technology Assessment Database; NHS EED, National Health Service Economic Evaluation Database; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
which reported the Burden of Infection as measured by Primary Antibody Deficiency (BIPAD-Q) symptom score in primary antibody deficiency (immunocompromised) patients with RSV (n = 41) and otherwise healthy controls with RSV (n = 38).The scale ranged from 0 (asymptomatic) to 7 (multiple, severe symptoms).In the healthy control group, the symptom score decreased by 0.143 in the 7-day period following RSV detection, compared with an increase of 0.469 in the primary antibody deficient group.
LRTIs compared with URTIs between November 2015 to December 2017 (53.1% vs. 46.9%;n = 46), whereas Gorcea et al.41 observed a higher rate of URTIs between December 2010 and February 2015 (69.6% vs. 30.4%;n = 23).Three studies reported on the economic burden of RSV in the immunocompromised.All three studies reported F I G U R E 4 Incidence of RSV in other high-risk groups.Italicised values were manually calculated; all data presented were collected as annual testing except for Morris et al.,47 which presented seasonal testing.Abbreviations: COVID-19, coronavirus-19; HSCT, haematopoietic stem-cell transplantation; NR, not reported; RSV, respiratory syncytial virus.
assessed the impact of the 2009 influenza pandemic on RSV testing behaviours, comparing the incidence of RSV detected from 2004-2015 and 2010-2015, and demonstrated similar RSV detection over these two periods, suggesting that no significant change occurred to viral testing behaviour as a result of the influenza pandemic.The growing awareness of the burden of RSV, as well as the advances in respiratory virus detection brought forward by the COVID-19 pandemic, 64 may potentially lead to improved RSV testing rates in the near future, providing a more accurate epidemiological picture of RSV.
Abbreviations: GP, general practice; ICU, intensive care unit; NHS, National Health Service; RSV, respiratory syncytial virus.a Inpatient stays include both hospital admission data and length of hospital stay.b Presence of symptoms refers to proportion of patients who display any symptoms of RSV.
Eligibility criteria for the SLR.
Abbreviations: A&E, accident and emergency; CCU, cardiac care unit; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; GP, general practice; HSCT, haematopoietic stem cell transplant; HTA, health technology assessment; ICU, intensive care unit; N/A, not applicable; O2, oxygen; RSV, respiratory syncytial virus; SLR, systematic literature review; TCU, transitional care unit; UK, United Kingdom.a Severe disease to be classified as RSV requiring hospitalisation or resulting in death; symptomatic disease to be classified as RSV showing signs/ symptoms, including RSV resulting in healthcare resource use e.g., GP appointments, or treatment.
None of the studies reported data regarding the epidemiology of respiratory complications of RSV.Economic outcomes included only direct resource use under both inpatient and outpatient settings and no studies reported any indirect resource use or disease-related costs.
14,15,55,59,60Morbey et al.59found 0.771 weekly RSV-attributable GP consultations in a modelled cohort of 10,000 patients (1,710 of them aged ≥65 years), in England during a winter season (Weeks 40 to 20).Fleming et al.4reported the mean number of GP episodes per average season attributable to RSV across the UK as 175,070 in patients ≥65 years, com- to the proportion of patients who display certain RSV symptoms (this included cough, weakness, shortness of breath, sputum, wheezing, fever, sore throat, headache, chest pain, vomiting, fatigue and myalgia).
Abbreviations: GP, general practice; ICU, intensive care unit; NHS, National Health Service; RSV, respiratory syncytial virus.a Inpatient stays include both hospital admission data and length of hospital stay.b Presence of symptoms refers to proportion of patients who display any symptoms of RSV.c Specific symptoms refer